Similar Datasets
Project description:Here we studied cellular level changes of hippocampal cells by unbiased single cell RNA-seq using AD mouse models bearing amyloid pathology (PS2APP), or amyloid and tau combined pathology (TauPS2APP) by single cell RNA-seq. We identified 16 different cell types and further characterized responses of microglia, oligodendrocytes, astrocytes and T cells to amyloidosis only and amyloid plus tau combined pathology. Both mouse models exhibited robust microglial responses. We also found distinct responses of oligodendrocytes to different AD pathologies. We observed increased T cell numbers in both mouse models. Current dataset presents diverse transcriptomic responses to AD pathology and provides resources to study molecular mechanisms underlying disease onset and progression.
2021-11-12 | GSE181786 | GEO
Project description:Amyloid plaques and neurofibrillary tangles are present in the brains of individuals with intact memory function. The study of these brains can open new avenues to identify new therapeutic targets. This experriment aimed to identified genes contributing to maintain an intact memory in the presence of AD pathology.
2020-05-07 | GSE147434 | GEO
Project description:Alzheimer’s disease (AD) is the major cause of dementia prevalent in older adults and with a high incidence in females; thus, Identification of early biomarkers is important for preventive interventions. To show potential early biomarkers, we carried out RNA-Sequencing analysis for 4-month(pre-pathology) TgF344-AD rats, a transgenic Alzheimer’s model that exhibits age-dependent AD progression. Our study showed two potential early biomarker genes (early growth response 2 (EGR2) and histone H2AA (HISIT1H2AA)) for AD, in the hippocampus of 4-month TgF344-AD females compared to wild-type littermates. Furthermore, due to the multifactorial cause for AD, we tested the therapeutic benefit of a multi-target approach using a co-treatment with diazoxide (DZ), a potassium channel activator, and dibenzoylmethane (DIB), which inhibits eIF2α-P activity, on TgF344-AD female. Our results strongly support the DZ/DIB-treatment as potential strategy to mitigate AD pathology due to its multi-target approach.
2023-11-22 | GSE245979 | GEO
Project description:Cerebral amyloid angiopathy (CAA) is an age-related condition and a major cause of intracerebral hemorrhage and cognitive decline that shows close links with Alzheimer's disease (AD). CAA is characterized by the aggregation of amyloid-β (Aβ) peptides and formation of Aβ deposits in the brain vasculature resulting in a disruption of the angioarchitecture. Capillaries are a critical site of Aβ pathology in CAA type 1 and become dysfunctional during disease progression. Here, applying an advanced protocol for the isolation of parenchymal microvessels from post-mortem brain tissue combined with liquid chromatography tandem mass spectrometry (LC-MS/MS), we determined the proteomes of CAA type 1 cases (n = 12) including a patient with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), and of AD cases without microvascular amyloid pathology (n = 13) in comparison to neurologically healthy controls (n = 12).
2022-02-16 | PXD029380 | Pride
Project description:Differences in gene expression between unsorted adipose tissue-derived mesenchymal stem cells (AD-MSCs), and a specific subpopulation that has been selected for the expression of the surface marker CD271. It is believed that the selection of this specific subpopulation from the heterogeneous SVF will lead to mesenchymal stem cells with higher angiogenetic potential.
2021-01-27 | E-MTAB-8740 | biostudies-arrayexpress
Project description:Alzheimer’s disease (AD) is the most common neurodegenerative pathology affecting more than 20 million people worldwide and the leading cause of dementia. Although AD neuropathology has been well defined, the underlying causes of the disease remain debatable. Recently, sex and gender are emerging as crucial drivers of development and progression of AD dementia. So, to investigate the molecular basis of gender¬related influences on the pathology of AD, we analyzed hippocampal brain tissues from control (CTR) and Alzheimer’s Disease (AD) patients using an integrated proteomic, metabolomics and transcriptomic approach. A principal component analysis carried out to identify major differences among the two datasets highlights differences among AD and CTR. Focusing on the gender dependent omic changes, comparative analyses were carried out considering males (M) and females (F) as separate subgroups in AD patients and in healthy subjects. The analysis was conducted considering proteins differentially expressed if they were present only in one condition or showed significant t¬test difference. The results strongly suggest that there is a significant difference between male and female in all the omic data sets either in the neurodegenerative disease and in the control. Preliminary results from bioinformatics analysis highlight major differences in energetic metabolism, cytoskeleton organization and oxidative stress response.The results are of main relevance for future clinical interventions that can reduce dementia risk in both male and female patients.
2024-10-01 | PXD034137 | Pride
Project description:Treatment strategies that are efficient against established Alzheimer's disease (AD) are needed. BRICHOS is a molecular chaperone domain that prevents amyloid fibril formation and associated cellular toxicity. In this study, we treated an AD mouse model seven months after pathology onset, using intravenous administration of recombinant human (rh) Bri2 BRICHOS R221E. Two injections of rh Bri2 BRICHOS R221E per week for three months in AD mice reduced amyloid b (Ab) burden, and mitigated astro- and microgliosis, as determined by glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba1) immunohistochemistry. Sequencing of RNA from cortical microglia cells showed that BRICHOS treatment normalized expression of identified plaque-induced genes in mice and humans, including clusterin and GFAP. Rh Bri2 BRICHOS R221E passed the blood-brain barrier (BBB) in age-matched wildtype mice as efficiently as in the AD mice, but then had no effect on measures of AD-like pathology, and mainly affected the expression of genes involved in cellular shape and movement. These results indicate a potential of rh Bri2 BRICHOS against advanced AD and underscore the ability of BRICHOS to target amyloid-induced pathology.
2024-09-25 | GSE263166 | GEO
Project description:Very little studies have explored the role played by the specialized choroid plexus epithelial cells and the ependymal cells that line the ventricles. In normal and pathological (AD) ageing, reports of alterations in the blood brain CSF barrier (BCSFB) integrity and membrane transporters, accompanied by deficiencies in CSF production and an enlarged ventricular volume have been documented. The molecular sequelae of events driving these age-related pathological changes remains elusive. Given the pivotal role of the ventricular system in normal brain physiology, in this study we proposed to explore their contributing role towards AD pathogenesis. To address this, we used our state-of-the-art proteomic platform, a liquid chromatography/mass spectrometry (LC-MS) approach coupled with Tandem Mass Tag labeling technology to conduct a detailed characterization and assessment of molecular changes in protein expression levels from isolated tissue from the walls of the ventricles in autopsy AD cases, and two groups of age-matched control cases (non-agenarian’s with no AD pathology, and those with no clinical AD diagnosis but significant amyloid pathology and Braak staging).
2021-09-08 | PXD012059 | Pride
Project description:Transgenic mouse models have been widely used to investigate the pathology of Alzheimer’s disease (AD). To elucidate underlying mechanisms of AD pathogenesis by amyloid beta (Aβ) and tau, we have generated a novel animal model of AD; ADLP - APT mice (Alzheimer’s Disease-Like Pathology) – carrying mutations of human amyloid precursor protein (APP), human presenilin-1 (PS1) and human tau. We profiled 9,824 proteins in the hippocampus of ADLP model mice using quantitative proteomics. To identify functional signatures in pathology of ADLP - APT mice, in-depth bioinformatics analysis was performed. For a longitudinal change of differentially expressed proteins (DEPs), we identified ADLP - APT mice hippocampal proteome in an age-dependent manner. Network maps of interactome between Aβ and tau in newly generated ADLP - APT mice reveal relationship between accelerated NFT pathology of AD and proteomic changes.
2018-01-25 | PXD006214 | Pride
Project description:The hippocampus is a primary region affected in Alzheimer’s disease (AD). Because AD postmortem brain tissue is not available prior to symptomatic stage, we lack understanding of early cellular pathogenic mechanisms. To address this issue, we examined the cellular origin and progression of AD pathogenesis in patient-based model systems including iPSC-derived brain cells transplanted into the mouse brain hippocampus, as well as human post-mortem hippocampal tissues. Our data showcase patient-based models to study the cellular origin, progression, and prion-like spread of AD pathogenesis.
2023-10-24 | PXD042229 | Pride